5-13913776-A-G

Position:

chr5-13913776-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369.3(DNAH5):c.1503T>C(p.Ile501Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,612,792 control chromosomes in the GnomAD database, including 132,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15311 hom., cov: 32)

Exomes 𝑓: 0.39 ( 117302 hom. )

Consequence

DNAH5
NM_001369.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.487

Variant links:

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 links:

DNAH5 (HGNC:):

DNAH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 5-13913776-A-G is Benign according to our data. Variant chr5-13913776-A-G is described in ClinVar as [Benign]. Clinvar id is 163158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13913776-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.487 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.1503T>C	p.Ile501Ile	synonymous_variant	11/79	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.1503T>C	p.Ile501Ile	synonymous_variant	11/79	1	NM_001369.3	ENSP00000265104.4		Q8TE73

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66360

AN:

151726

Hom.:

15307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.421

AC:

105718

AN:

251072

Hom.:

24495

AF XY:

0.414

AC XY:

56187

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.537

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.861

Gnomad SAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

AF:

0.391

AC:

571673

AN:

1460948

Hom.:

117302

Cov.:

AF XY:

0.389

AC XY:

283053

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.841

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.437

AC:

66391

AN:

151844

Hom.:

15311

Cov.:

AF XY:

0.436

AC XY:

32333

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.530

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.390

Hom.:

13522

Bravo

AF:

0.451

Asia WGS

AF:

0.575

AC:

1997

AN:

3476

EpiCase

AF:

0.384

EpiControl

AF:

0.382

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ile501Ile in exon 11 of DNAH5: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 47.1% (2076/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3213936). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 26, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Primary ciliary dyskinesia 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.83

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over